BACKGROUND: Short-term studies in adolescents have generally shown an
enhancement of calcium absorption by inulin-type fructans. Results have
been inconsistent; however, and no studies have been conducted to
determine whether this effect persists with long-term use. OBJECTIVE:
The objective was to assess the effects on calcium absorption and bone
mineral accretion after 8 wk and 1 y of supplementation with an
inulin-type fructan. DESIGN: Pubertal adolescents were randomly
assigned to receive 8 g/d of a mixed short and long degree of
polymerization inulin-type fructan product (fructan group) or
maltodextrin placebo (control group). Bone mineral content and bone
mineral density were measured before randomization and after 1 y.
Calcium absorption was measured with the use of stable isotopes at
baseline and 8 wk and 1 y after supplementation. Polymorphisms of the
Fok1 vitamin D receptor gene were determined. RESULTS: Calcium
absorption was significantly g reater in the fructan group than in the
control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1
y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1
genotype was present such that subjects with an ff genotype had the
least initial response to fructan. After 1 y, the fructan group had a
greater increment in both whole-body bone mineral content (difference:
35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference:
0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group.
CONCLUSION: Daily consumption of a combination of prebiotic short- and
long-chain inulin-type fructans significantly increases calcium
absorption and enhances bone mineralization during pubertal growth.
Effects of dietary factors on calcium absorption may be modulated by
genetic factors, including specific vitamin D receptor gene
polymorphisms.
BACKGROUND & AIMS: Long-term data on the risk of colorectal cancer
according to dose, duration, and consistency of aspirin therapy are
limited. METHODS: We conducted a prospective study of 47,363 male
health professionals who were ages 40-75 years at enrollment in 1986.
Biennially, we collected data on aspirin use, other risk factors, and
diagnoses of colorectal cancer. We confirmed all reports of colorectal
cancer through 2004 by review of medical records. RESULTS: During 18
years of follow-up, we documented 975 cases of colorectal cancer over
761,757 person-years. After adjustment for risk factors, men who
regularly used aspirin (>/=2 times per week) had a multivariate
relative risk (RR) for colorectal cancer of 0.79 (95% confidence
interval, [CI], 0.69-0.90) compared with nonregular users. However,
significant risk reduction required at least 6-10 years of use (P for
trend = .008) and was no longer evident within 4 years of discontinuing
use (multivariat e RR, 1.00; CI, 0.72-1.39). The benefit appeared
related to increasing cumulative average dose: compared with men who
denied any aspirin use, the multivariate RRs for cancer were 0.94 (CI,
0.75-1.18) for men who used 0.5-1.5 standard aspirin tablets per week,
0.80 (CI, 0.63-1.01) for 2-5 aspirin tablets per week, 0.72 (CI,
0.56-0.92) for 6-14 aspirin tablets per week, and 0.30 (CI, 0.11-0.81)
for >14 aspirin tablets per week (P for trend = .004). CONCLUSIONS:
Regular, long-term aspirin use reduces risk of colorectal cancer among
men. However, the benefit of aspirin necessitates at least 6 years of
consistent use, with maximal risk reduction at doses greater than 14
tablets per week. The potential hazards associated with long-term use
of such doses should be carefully considered.
While the fundamental metabolic function of calcium is to serve as a
second messenger, coupling intracellular responses to extracellular
signals, nutritional deficiency of calcium is manifested at a higher
level of organization: 1) depletion of the calcium nutrient reserve; 2)
inadequate complexation of digestive byproducts; and 3) collateral
effects of hormones produced primarily to compensate for low calcium
intake. The first mechanism contributes to the osteoporosis problem,
the second to kidney stones and colon cancer, and the third to
hypertension, preeclampsia, obesity, and insulin resistance, among
others. Adequate calcium intakes (1000-1500 mg/d) in adults have been
shown in controlled trials to lower the risk of osteoporotic fractures,
kidney stones, obesity, and hypertension. The best source of calcium is
dairy foods, largely because the disorders concerned depend upon
multiple nutrients, not just calcium, and dairy provides a broad array
of essential nu trients in addition to calcium, and at low cost.
ACKGROUND AND AIMS: The intestinal microbiota play a pivotal role in
the inflammation associated with Crohn's disease through their
interaction with the mucosal immune system. Some bifidobacteria species
are immunoregulatory and induce increased dendritic cell interleukin 10
(IL-10) release in vitro. Fructo-oligosaccharides (FOS) increase faecal
and mucosal bifidobacteria in healthy volunteers. The aim of this study
was to assess the effect of FOS administration on disease activity,
bifidobacteria concentrations, and mucosal dendritic cell function in
patients with moderately active Crohn's disease. PATIENTS AND METHODS:
Ten patients with active ileocolonic Crohn's disease received 15 g of
FOS for three weeks. Disease activity was measured using the Harvey
Bradshaw index. Faecal and mucosal bifidobacteria were quantified by
fluorescence in situ hybridisation, and mucosal dendritic cell IL-10
and Toll-like receptor (TLR) expression were assessed by flow cytometry
of dissociated rectal biopsies. RESULTS: FOS induced a significant
reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 6.9 (3.4)
(p < 0.01). There was a significant increase in faecal
bifidobacteria concentration from 8.8 (0.9) log(10) to 9.4 (0.9)
log(10) cells/g dry faeces (p < 0.001). The percentage of IL-10
positive dendritic cells increased from 30 (12)% to 53 (10)% (p=0.06).
Finally, the percentage of dendritic cells expressing TLR2 and TLR4
increased from 1.7 (1.7)% to 36.8 (15.9)% (p=0.08) and from 3.6 (3.6)%
to 75.4 (3.4)% (p < 0.001), respectively. CONCLUSIONS: FOS
supplementation increases faecal bifidobacteria concentrations and
modifies mucosal dendritic cell function. This novel therapeutic
strategy appears to decrease Crohn's disease activity in a small open
label trial and therefore warrants further investigation.
BACKGROUND AND AIMS: The intestinal microbiota play a pivotal role in
the inflammation associated with Crohn's disease through their
interaction with the mucosal immune system. Some bifidobacteria species
are immunoregulatory and induce increased dendritic cell interleukin 10
(IL-10) release in vitro. Fructo-oligosaccharides (FOS) increase faecal
and mucosal bifidobacteria in healthy volunteers. The aim of this study
was to assess the effect of FOS administration on disease activity,
bifidobacteria concentrations, and mucosal dendritic cell function in
patients with moderately active Crohn's disease. PATIENTS AND METHODS:
Ten patients with active ileocolonic Crohn's disease received 15 g of
FOS for three weeks. Disease activity was measured using the Harvey
Bradshaw index. Faecal and mucosal bifidobacteria were quantified by
fluorescence in situ hybridisation, and mucosal dendritic cell IL-10
and Toll-like receptor (TLR) expression were assessed by flow cytometry
of dissociated rectal biopsies. RESULTS: FOS induced a significant
reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 6.9 (3.4)
(p < 0.01). There was a significant increase in faecal
bifidobacteria concentration from 8.8 (0.9) log(10) to 9.4 (0.9)
log(10) cells/g dry faeces (p < 0.001). The percentage of IL-10
positive dendritic cells increased from 30 (12)% to 53 (10)% (p=0.06).
Finally, the percentage of dendritic cells expressing TLR2 and TLR4
increased from 1.7 (1.7)% to 36.8 (15.9)% (p=0.08) and from 3.6 (3.6)%
to 75.4 (3.4)% (p < 0.001), respectively. CONCLUSIONS: FOS
supplementation increases faecal bifidobacteria concentrations and
modifies mucosal dendritic cell function. This novel therapeutic
strategy appears to decrease Crohn's disease activity in a small open
label trial and therefore warrants further investigation.
A role for colonic sulfide in the pathogenesis and treatment of
ulcerative colitis (UC) has emerged based on biochemical,
microbiological, nutritional, toxicological, epidemiological, and
therapeutic evidence. Metabolism of isolated colonic epithelial cells
has indicated that the bacterial short-chain fatty acid n-butyrate
maintains the epithelial barrier and that sulfides can inhibit
oxidation of n-butyrate analogous to that observed in active UC. Sulfur
for fermentation in the colon is essential for n-butyrate formation and
sulfidogenesis aids disposal of colonic hydrogen produced by bacteria.
The numbers of sulfate-reducing bacteria and sulfidogenesis is greater
in UC than control cases. Sulfide is mainly detoxified by methylation
in colonic epithelial cells and circulating red blood cells. The enzyme
activity of sulfide methylation is higher in red blood cells of UC
patients than control cases. Patients with UC ingest more protein and
thereby sulfur amino acid s than control subjects. Removing foods rich
in sulfur amino acids (milk, eggs, cheese) has proven therapeutic
benefits in UC. 5-Amino salicylic acid reduces fermentative production
of hydrogen sulfide by colonic bacteria, and aminoglycosides, which
inhibit sulfate-reducing bacteria, are of therapeutic benefit in active
UC. Methyl-donating agents are a category of drugs of potential
therapeutic use in UC. A correlation between sulfide production and
mucosal immune responses in UC needs to be undertaken. Control of
sulfidogenesis and sulfide detoxification may be important in the
disease process of UC, although whether their roles is in an initiating
or promoting capacity has yet to be determined.
In humans, there is increasing evidence that the colon can absorb
nutritionally significant amounts of calcium, and this process may be
susceptible to dietary manipulation by fermentable substrates,
especially inulin-type fructans. Inulin-type fructans can modulate
calcium absorption because they are resistant to hydrolysis by
mammalian enzymes and are fermented in the large intestine to produce
short-chain fatty acids, which in turn reduce luminal pH and modify
calcium speciation, and hence solubility, or exert a direct effect on
the mucosal transport pathway. Quite a few intervention studies showed
an improvement of calcium absorption in adolescents or young adults by
inulin-type fructans. In the same way, a positive effect has been
reported in older women.
Patients with irritable bowel syndrome (IBS) often request dietary
recommendations. They must eat, and they want to know what to eat.
Present national guidelines recommend dietary treatment with fiber for
IBS patients with constipation. Diet recommendations are made based on
symptoms. There may be different dietary recommendations for
constipation, diarrhea, and pain or bloating. This article reviews the
relationship of foods to IBS and issues of food intolerances and
hypersensitivities, and recommendations for diet therapy. The role of
dietary fiber, both soluble and insoluble, is reviewed. Although there
are few studies to substantiate exact diets, broad dietary plans are
recommended for the different symptoms of IBS. In addition, the recent
literature on probiotics and prebiotics pertinent to IBS is reviewed.
Colon cancer remains a significant global health concern. The impact of
specific dietary components on colon tissue likely depends on a host of
genomic processes that influence the growth, development, and
differentiation of the epithelial cells at the colon crypt surface,
where the balance between proliferation and differentiation is
maintained possibly through the Wnt (beta-catenin/T-cell factor)
signaling pathway. A loss of balance caused by either genetic mutations
or environmental factors such as dietary habits can modulate the risk
for the formation of aberrant crypt foci and ultimately the development
of colon cancer. Evidence exists that butyrate reduces the number and
the size of aberrant crypt foci in the colon. Butyrate is a natural
histone deacetylase inhibitor as well as a molecule involved with
enhanced TGF-beta-induced SMAD3 phosphorylation, increased
IFN-gamma-mediated apoptosis, and altered expression of the intestinal
muc2 gene that is responsibl e for mucin synthesis. Other dietary
components, such as vitamin D and (n-3) fatty acids, may regulate
proliferative properties of colon progenitor cells as well as the
differentiation of subcellular lineages. Although these findings are
intriguing, there are uncertainties that remain to be resolved
including the optimal exposure needed to bring about an effect, the
appropriate timing of administration, and if nutrient-nutrient and
nutrient-gene interactions determine the overall response. The expanded
use of high-throughput technologies, knowledge about the expression of
genes and protein fingerprints, and metabolomic profiling will assist
in addressing these issues and ultimately in determining the
physiological significance of bioactive food components as cancer
protectants.
Nondigestible oligosaccharides (NDOs) have been found to stimulate
absorption of several minerals and to improve mineralization of bone.
Hence, these substances are potential ingredients for "functional
foods." In addition to a nutritional effect, functional foods have
physiologic and psychological benefits that result in improved health
or reduced risk of chronic disease. Most of the scientific evidence for
the functional effects of NDOs is based on animal experiments in which
NDOs increased the availability of calcium, magnesium, zinc, and iron.
This stimulatory effect of some NDOs is assumed to be mainly due to
their prebiotic character. A prebiotic is defined as a substrate or
food ingredient that is nondigestible for the host but is fermented
selectively by some of the intestinal microflora. Thus, it stimulates
the growth and activity of bacteria with beneficial consequences for
the host's health. Recently, these findings were confirmed in human
studies for s ome NDOs. The effects seem to be specific for the type of
carbohydrate and are likely related to the rate of fermentation by the
intestinal flora and appear to depend on the ingested dose.
Contradictory results of the effect of prebiotics in literature may be
due to the experimental design because the effect of NDOs depends on
the dose, the time of administration, the content of calcium in the
diet, the part of the skeleton investigated, and the age of the
subjects studied.
Human subjects and their enteric microbiota have evolved together to
reach a state of mutual tolerance. Mounting evidence from both animal
models and human studies suggests that inflammatory bowel disease (IBD)
represents a malfunction of this relationship. The enteric microecology
therefore represents an attractive therapeutic target with few side
effects. Probiotics and prebiotics have been investigated in clinical
trials as treatments for IBD, with conflicting results. The evidence
for the use of probiotics in the management of pouchitis is persuasive
and several studies indicate their effectiveness in ulcerative colitis.
Trials of probiotics and prebiotics in Crohn's disease are less
convincing. However, methodologies vary widely and a range of
probiotic, prebiotic and combination (synbiotic) treatments have been
tested in a variety of patient groups with an assortment of end points.
Conclusions about any one treatment in a specific patient group can
therefore only be drawn on evidence from relatively small numbers of
patients. The present article reviews the role of the intestinal
microbiota in the pathogenesis of IBD and addresses the clinical
evidence for the therapeutic manipulation of bowel microbiota using
probiotics, prebiotics and synbiotics in IBD.
The microbiota of the human intestinal tract play an important role in
health, in particular by mediating many of the effects of diet upon gut
health. Surveys of 16S rRNA sequence diversity in the human colon have
emphasized the low proportion of sequences that match cultured
bacterial species. This may reflect limited recent effort on
cultivation rather than inherent unculturability, however, as anaerobic
isolation methods can apparently recover a wide range of the diversity
found. A combination of information from representative cultures,
molecular tools for enumeration and tracking of bacterial metabolites
offers the most powerful route to understanding the roles played by
different groups of bacteria in the gut ecosystem. Progress is being
made for example in defining key functional groups including primary
colonizers of insoluble dietary substrates, and major contributors to
metabolites such as butyrate that influence the health of the gut
mucosa. There is in creasing evidence that bacterial populations in the
large intestine respond to changes in diet, in particular to the type
and quantity of dietary carbohydrate. A general consequence of
increased carbohydrate consumption is to reduce the pH of the gut
lumen, which is likely to play a major role in determining bacterial
metabolism and competition. Oligosaccharides used as dietary prebiotics
must inevitably have complex effects upon the bacterial community that
include non-target organisms and the consequences of metabolic
cross-feeding and changes in the gut environment.
Nondigestible oligosaccharides have been shown to increase the
absorption of several minerals (calcium, magnesium, in some cases
phosphorus) and trace elements (mainly copper, iron, zinc). Inulin-type
fructans including oligofructose and fructooligosaccharides derived
from sucrose by enzymatic transfructosylation are the best investigated
food ingredients in this respect. The stimulation of absorption was
more pronounced when the demand for calcium was high, i.e., in animals
in the rapid growing stage and in animals with impaired calcium
absorption because of either ovariectomy or gastrectomy. Even a small
stimulation of calcium absorption increased the mineral accumulation in
the skeleton because of its persisting effect over months. Inulin-type
fructans stimulated mineral absorption and bone mineral accretion when
combined with probiotic lactobacilli and in the presence of
antibiotics. Direct comparison of different inulin-type fructans
revealed a more pronounced effect by inulin or a mixture of long-chain
inulin and oligofructose than by oligofructose alone. Mechanisms on how
inulin-type fructans mediate this effect include acidification of the
intestinal lumen by short-chain fatty acids increasing solubility of
minerals in the gut, enlargement of the absorption surface, increased
expression of calcium-binding proteins mainly in the large intestine,
modulated expression of bone-relevant cytokines, suppression of bone
resorption, increased bioavailability of phytoestrogens, and, via
stimulation of beneficial commensal microorganisms, increase of calcium
uptake by enterocytes. Under certain conditions, inulin-type fructans
may improve mineral absorption by their impact on the amelioration of
gut health including stabilization of the intestinal flora and
reduction of inflammation. The abundance of reports indicate that
inulin-type fructans are promising substances that could help to
improve the supply with available calcium in human nutrition and by
this contribute to bone health.
Crohn's disease and ulcerative colitis, also called chronic
inflammatory bowel diseases (IBD), affect up to 500 per 100,000 persons
in the Western world. Recent studies in the etiology of IBD suggest
that these diseases are caused by a combination of genetic,
environmental, and immunological factors. Results from humans and
especially animal models of colitis reported by our group and others
have indicated that these diseases result from a lack of tolerance to
resident intestinal bacteria in genetically susceptible hosts.
Probiotic bacteria have health-promoting effects for the host when
ingested and have also shown efficacy in ulcerative colitis and
refractory pouchitis. In light of the efficacy of providing probiotic
bacteria to patients with IBD, there has been interest in the
prophylactic and therapeutic potential of inulin, oligofructose, and
other prebiotics for patients with or at risk of IBD. Prebiotics are
nondigestible dietary oligosaccharides that affec t the host by
selectively stimulating growth, activity, or both of selective
intestinal (probiotic) bacteria. Prebiotics are easy to administer and,
in contrast to probiotic therapy, do not require administration of
large amounts of (live) bacteria and are therefore easier to
administer. Studies using prebiotics, especially beta-fructan
oligosaccharides, for the treatment of chronic intestinal inflammation
have shown benefit in animal models of colitis. Studies using these
prebiotics alone or in combination with probiotics are emerging and
have shown promise. These dietary therapies could lead to novel
treatments for these chronic debilitating diseases.
Crohn's disease and ulcerative colitis, also called chronic
inflammatory bowel diseases (IBD), affect up to 500 per 100,000 persons
in the Western world. Recent studies in the etiology of IBD suggest
that these diseases are caused by a combination of genetic,
environmental, and immunological factors. Results from humans and
especially animal models of colitis reported by our group and others
have indicated that these diseases result from a lack of tolerance to
resident intestinal bacteria in genetically susceptible hosts.
Probiotic bacteria have health-promoting effects for the host when
ingested and have also shown efficacy in ulcerative colitis and
refractory pouchitis. In light of the efficacy of providing probiotic
bacteria to patients with IBD, there has been interest in the
prophylactic and therapeutic potential of inulin, oligofructose, and
other prebiotics for patients with or at risk of IBD. Prebiotics are
nondigestible dietary oligosaccharides that affect the host by
selectively stimulating growth, activity, or both of selective
intestinal (probiotic) bacteria. Prebiotics are easy to administer and,
in contrast to probiotic therapy, do not require administration of
large amounts of (live) bacteria and are therefore easier to
administer. Studies using prebiotics, especially beta-fructan
oligosaccharides, for the treatment of chronic intestinal inflammation
have shown benefit in animal models of colitis. Studies using these
prebiotics alone or in combination with probiotics are emerging and
have shown promise. These dietary therapies could lead to novel
treatments for these chronic debilitating diseases.
Diet modulates immune functions in different ways and affects host
resistance to infections. In addition to the essential nutrients in
food, nonessential food constituents such as nondigestible
carbohydrates also affect the immune system. First results from human
intervention studies suggest that the intake of inulin (IN) and
oligofructose (OF) has beneficial effects on the gut-associated
lymphoid tissue. At the level of the systemic immune system, however,
only minor effects have been observed in healthy adult human subjects.
In contrast, data from studies with infants suggest that
supplementation with a prebiotic mixture positively affects postnatal
immune development and increases fecal secretory IgA. Animal studies
confirm the observations from human trials and give more insight into
the immune tissue- specific effects of IN/OF. A clear outcome of the
animal studies is that the intestinal immune system and especially the
immune cells associated with the Peyer's patches are responsive to a
dietary supplement of IN/OF and/or their metabolites. The mechanisms of
IN/OF include indirect effects such as a shift in the composition of
the intestinal flora and the enhanced production of immunoregulatory
SCFA and perhaps other bacterial metabolites. Few data suggest direct
effects of IN/OF via carbohydrate receptors on intestinal epithelial
cells and immune cells. In conclusion, prebiotic IN/OF clearly modulate
immunological processes at the level of the gut-associated lymphoid
tissue, which may be associated with significant health benefits in
infants and patients with intestinal inflammatory diseases.
The bacteria colonizing the human intestinal tract exhibit a high
phylogenetic diversity that reflects their immense metabolic potential.
By virtue of their catalytic activity, the human gut micro-organisms
have an impact on gastrointestinal function and host health. All
dietary components that escape digestion in the small intestine are
potential substrates of the bacteria in the colon. The bacterial
conversion of carbohydrates, proteins and nonnutritive compounds such
as polyphenolic substances leads to the formation of a large number of
compounds that may have beneficial or adverse effects on human health.
PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic
function and disease patterns. RECENT FINDINGS: Topical nutrients are
preferentially used by the gut mucosa to maintain structure and
function. With the colon, topical nutrients are generated by the
colonic microbiota to maintain mucosal health. Most importantly, short
chain fatty acids control proliferation and differentiation, thereby
reducing colon cancer risk. In patients with massive loss of small
intestine, short chain fatty acid production supports survival by
releasing up to 1000 kcal energy/day. Human studies show that the
microbiota synthesizes a large pool of utilizable folate which may
support survival in impoverished populations. Unfortunately, the
microbiota may also elaborate toxic products from food residues such as
genotoxic hydrogen sulfide by sulfur-reducing bacteria in response to a
high-meat diet. The employment of culture-free techniques based on 16S
regions of DNA has re vealed that our colons harbor over 800 bacterial
species and 7000 different strains. Evidence suggests that the diet
directly influences the diversity of the microbiota, providing the link
between diet, colonic disease, and colon cancer. The microbiota,
however, can determine the efficiency of food absorption and risk of
obesity. SUMMARY: Our investigations have focused on a small number of
bacterial species: characterization of microbiota and its metabolism
can be expected to provide the key to colonic health and disease.
The human gut microbiota plays a significant role in human health
through its ability to digest food ingredients and manufacture
metabolites. This can be positive or negative for host welfare.
Moreover, the microflora plays an active role in host defense whereby
colonization resistance affords protection against pathogens.
Prebiotics are nondigestible food ingredients that target beneficial
components of the gut microflora (mainly colonic), particularly the
bifidobacteria. In vitro and in vivo evidence has accumulated to
confirm the prebiotic effects of inulin-derived fructans.
In genetically susceptible individuals, an altered mucosal immune
response against some commensal bacteria of the gut ecosystem appears
to be the principal mechanism leading to intestinal lesions in
inflammatory bowel disease (IBD). The information currently available
does not provide an exact explanation about the origin of this
important dysfunction of the interaction between host and commensal
bacteria, but an altered microbial composition has been detected in the
gut ecosystem of patients with Crohn's disease or ulcerative colitis.
Prebiotics are food ingredients not digested nor absorbed in the upper
intestinal tract that are fermented by intestinal bacteria in a
selective way promoting changes in the gut ecosystem. Experimental and
human studies have shown that inulin and oligofructose stimulate
saccharolysis in the colonic lumen and favour the growth of indigenous
lactobacilli and bifidobacteria. These effects are associated with
reduced mucosal inflammatio n in animal models of IBD. Strong
experimental evidence supports the hypothesis that inulin and
oligofructose can offer an opportunity to prevent or mitigate
intestinal inflammatory lesions in human Crohn's disease, ulcerative
colitis, and pouchitis. Encouraging results have been obtained in
preliminary clinical trials.
Several studies in animals and humans have shown positive effects of
nondigestible oligosaccharides (NDO) on mineral absorption and
metabolism and bone composition and architecture. These include inulin,
oligofructose, fructooligosaccharides, galactooligosaccharides, soybean
oligosaccharide, and also resistant starches, sugar alcohols, and
difructose anhydride. A positive outcome of dietary prebiotics is
promoted by a high dietary calcium content up to a threshold level and
an optimum amount and composition of supplemented prebiotics. There
might be an optimum composition of fructooligosaccharides with
different chain lengths (synergy products). The efficacy of dietary
prebiotics depends on chronological age, physiological age, menopausal
status, and calcium absorption capacity. There is evidence for an
independent probiotic effect on facilitating mineral absorption.
Synbiotics, i.e., a combination of prebiotics and prebiotics, can
induce additional effects. Whether a low content of habitual NDO would
augment the effect of dietary prebiotics or synbiotics remains to be
studied. The underlying mechanisms are manifold: increased solubility
of minerals because of increased bacterial production of short-chain
fatty acids, which is promoted by the greater supply of substrate; an
enlargement of the absorption surface by promoting proliferation of
enterocytes mediated by bacterial fermentation products, predominantly
lactate and butyrate; increased expression of calcium-binding proteins;
improvement of gut health; degradation of mineral complexing phytic
acid; release of bone-modulating factors such as phytoestrogens from
foods; stabilization of the intestinal flora and ecology, also in the
presence of antibiotics; stabilization of the intestinal mucus; and
impact of modulating growth factors such as polyamines. In conclusion,
prebiotics are the most promising but also best investigated substances
with respect to a bone-health-promoting potential, compared with
probiotics and synbiotics. The results are more prominent in animal
models, where more studies have been performed, than in human studies,
where experimental conditions are more difficult to control.
Several studies in animals and humans have shown positive effects of
nondigestible oligosaccharides (NDO) on mineral absorption and
metabolism and bone composition and architecture. These include inulin,
oligofructose, fructooligosaccharides, galactooligosaccharides, soybean
oligosaccharide, and also resistant starches, sugar alcohols, and
difructose anhydride. A positive outcome of dietary prebiotics is
promoted by a high dietary calcium content up to a threshold level and
an optimum amount and composition of supplemented prebiotics. There
might be an optimum composition of fructooligosaccharides with
different chain lengths (synergy products). The efficacy of dietary
prebiotics depends on chronological age, physiological age, menopausal
status, and calcium absorption capacity. There is evidence for an
independent probiotic effect on facilitating mineral absorption.
Synbiotics, i.e., a combination of probiotics and prebiotics, can
induce additional effects. Wheth er a low content of habitual NDO would
augment the effect of dietary prebiotics or synbiotics remains to be
studied. The underlying mechanisms are manifold: increased solubility
of minerals because of increased bacterial production of short-chain
fatty acids, which is promoted by the greater supply of substrate; an
enlargement of the absorption surface by promoting proliferation of
enterocytes mediated by bacterial fermentation products, predominantly
lactate and butyrate; increased expression of calcium-binding proteins;
improvement of gut health; degradation of mineral complexing phytic
acid; release of bone-modulating factors such as phytoestrogens from
foods; stabilization of the intestinal flora and ecology, also in the
presence of antibiotics; stabilization of the intestinal mucus; and
impact of modulating growth factors such as polyamines. In conclusion,
prebiotics are the most promising but also best investigated substances
with respect to a bone-health-promoting potential, compared with
probiotics and synbiotics. The results are more prominent in animal
models, where more studies have been performed, than in human studies,
where experimental conditions are more difficult to control.
A prebiotic is "a selectively fermented ingredient that allows specific
changes, both in the composition and/or activity in the
gastrointestinal microflora that confers benefits upon host well-being
and health." Today, only 2 dietary nondigestible oligosaccharides
fulfill all the criteria for prebiotic classification. The daily dose
of the prebiotic is not a determinant of the prebiotic effect, which is
mainly influenced by the number of bifidobacteria/g in feces before
supplementation of the diet with the prebiotic begins. The ingested
prebiotic stimulates the whole indigenous population of bifidobacteria
to growth, and the larger that population, the larger is the number of
new bacterial cells appearing in feces. The "dose argument" is thus not
supported by the scientific data: it is misleading for consumers and
should not be allowed. A prebiotic index is proposed, defined as "the
increase in the absolute number of bifidobacteria expressed divided by
the daily dose of prebiotic ingested."
PURPOSE OF REVIEW: This review summarizes the clinical efficacy of
probiotics and prebiotics in gastrointestinal disorders and examines
the mechanisms of action related to their therapeutic effect. RECENT
FINDINGS: The demonstration that immune and epithelial cells can
discriminate between different microbial species has extended the known
mechanism(s) of action of probiotics beyond simple barrier and
antimicrobial effects. It has also confirmed that probiotic bacteria
modulate mucosal and systemic immune activity and epithelial function.
The progressive unraveling of these mechanisms of action has led to new
credence for the use of probiotics and prebiotics in clinical medicine.
Level I evidence now exists for the therapeutic use of probiotics in
infectious diarrhea in children, recurrent Clostridium
difficile-induced infections and postoperative pouchitis. Level II
evidence is emerging for the use of probiotics in other
gastrointestinal infections, prevention of postoperative bacterial
translocation, irritable bowel syndrome, and in both ulcerative colitis
and Crohn disease. Nevertheless, one consistent feature has emerged
over the past year: Not all probiotic bacteria have similar therapeutic
effects. Future clinical trials will need to incorporate this fact into
trial planning and design. SUMMARY: The use of probiotics and
prebiotics as therapeutic agents for gastrointestinal disorders is
rapidly moving into the "mainstream." Mechanisms of action explain the
therapeutic effects and randomized; controlled trials provide the
necessary evidence for their incorporation into the therapeutic
armamentarium.
Probiotics have preventive as well as curative effects on several types
of diarrhea of different etiologies. Prevention and therapy (or
alleviation) of diarrhea have been successfully investigated for
numerous dietary probiotics to establish probiotic properties and to
justify health claims (the medicinal use of probiotic food and the
therapy of gastrointestinal diseases itself may not be advertised under
current food laws). Other probiotic microorganisms (e.g., Lactobacillus
rhamnosus GG, L. reuteri, certain strains of L. casei, L. acidophilus,
Escherichia coli strain Nissle 1917, and certain bifidobacteria and
enterococci (Enterococcus faecium SF68) as well as the probiotic yeast
Saccharomyces boulardii have been investigated with regard to their
medicinal use, either as single strains or in mixed-culture probiotics.
However, the effects on humans have been assessed mainly in smaller (n
< 100) randomized, controlled clinical studies or in open label
trials, but large intervention studies and epidemiological
investigations of long-term probiotic effects are largely missing.
Perhaps with the exception of nosocomial diarrhea or
antibiotic-associated diarrhea, the results of these studies are not
yet sufficient to give specific recommendations for the clinical use of
probiotics in the treatment of diarrhea.
Colorectal cancer (CRC) is the third most common form of cancer.
Current treatments including chemotherapy, radiotherapy and surgery are
all associated with a high risk of complications and are not always
successful, highlighting the need to develop new treatment strategies.
The ingestion of probiotics, prebiotics or combinations of both
(synbiotics) represents a novel new therapeutic option. Probiotics and
prebiotics act to alter the intestinal microflora by increasing
concentrations of beneficial bacteria such as lactobacillus and
bifidobacteria, and reducing the levels of pathogenic micro-organisms.
This strategy has the potential to inhibit the development and
progression of neoplasia via mechanisms including; decreased intestinal
inflammation, enhanced immune function and anti-tumorigenic activity,
binding to potential food carcinogens including toxins found in meat
products, and a reduction in bacterial enzymes which hydrolyse
precarcinogenic compounds, such as beta-glucuronidase. There is
substantial experimental evidence to suggest that probiotics and
prebiotics may be beneficial in the prevention and treatment of colon
cancer, however to date there have been few conclusive human trials.
Probiotics and prebiotics have the potential to impact significantly on
the development, progression and treatment of colorectal cancer and may
have a valuable role in cancer prevention.
BACKGROUND: Prebiotics are short-chain carbohydrates that alter the
composition, or metabolism, of the gut microbiota in a beneficial
manner. It is therefore expected that prebiotics will improve health in
a way similar to probiotics, whilst at the same time being cheaper, and
carrying less risk and being easier to incorporate into the diet than
probiotics. AIM: To review published evidence for prebiotic effects on
gut function and human health. METHODS: We searched the Science
Citation Index with the terms prebiotic, microbiota, gut bacteria,
large intestine, mucosa, bowel habit, constipation, diarrhoea,
inflammatory bowel disease, Crohn's disease, ulcerative colitis,
pouchitis, calcium and cancer, focussing principally on studies in
humans and reports in the English language. Search of the Cochrane
Library did not identify any clinical study or meta-analysis on this
topic. RESULTS: Three (Sources of Prebiotics), oligofructose,
galacto-oligosaccharides and lactulose, clearly alter the balance of
the large bowel microbiota by increasing bifidobacteria and
Lactobacillus numbers. These carbohydrates are fermented and give rise
to short-chain fatty acid and intestinal gas; however, effects on bowel
habit are relatively small. Randomized-controlled trials of their
effect in a clinical context are few, although animal studies show
anti-inflammatory effects in inflammatory bowel disease, while calcium
absorption is increased. CONCLUSIONS: It is still early days for
prebiotics, but they offer the potential to modify the gut microbial
balance in such a way as to bring direct health benefits cheaply and
safely.
BACKGROUND: Prebiotics are short-chain carbohydrates that alter the
composition, or metabolism, of the gut microbiota in a beneficial
manner. It is therefore expected that prebiotics will improve health in
a way similar to probiotics, whilst at the same time being cheaper, and
carrying less risk and being easier to incorporate into the diet than
probiotics. AIM: To review published evidence for prebiotic effects on
gut function and human health. METHODS: We searched the Science
Citation Index with the terms prebiotic, microbiota, gut bacteria,
large intestine, mucosa, bowel habit, constipation, diarrhoea,
inflammatory bowel disease, Crohn's disease, ulcerative colitis,
pouchitis, calcium and cancer, focussing principally on studies in
humans and reports in the English language. Search of the Cochrane
Library did not identify any clinical study or meta-analysis on this
topic. RESULTS: Three prebiotics, oligofructose,
galacto-oligosaccharides and lactulose, clearly alter the balance of
the large bowel microbiota by increasing bifidobacteria and
Lactobacillus numbers. These carbohydrates are fermented and give rise
to short-chain fatty acid and intestinal gas; however, effects on bowel
habit are relatively small. Randomized-controlled trials of their
effect in a clinical context are few, although animal studies show
anti-inflammatory effects in inflammatory bowel disease, while calcium
absorption is increased. CONCLUSIONS: It is still early days for
prebiotics, but they offer the potential to modify the gut microbial
balance in such a way as to bring direct health benefits cheaply and
safely.
The terms intestinal "microflora" or "microbiota refer to the microbial
ecosystem colonizing the gastrointestinal tract. Recently developed
molecular biology instruments suggest that a substantial part of
bacterial communities within the human gut still have to be described.
The relevance and impact of resident bacteria on the host physiology
and pathology are, however, well documented. The main functions of
intestinal microflora include (1) metabolic activities translating into
energy and nutrients uptake, and (2) host protection against invasion
by foreign microorganisms. Intestinal bacteria play an essential role
in the development and homeostasis of the immune system. Lymphoid
follicles within the intestinal mucosa are the main areas for immune
system induction and regulation. On the other hand, there is evidence
implicating intestinal microbiota in certain pathological processes
including multi-organ failure, colon cancer, and inflammatory bowel
disease.
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a significant
gastrointestinal disorder with unknown etiology. The symptoms can
greatly weaken patients' quality of life and account for notable
economical costs for society. Contribution of the gastrointestinal
microbiota in IBS has been suggested. Our objective was to characterize
putative differences in gastrointestinal microbiota between patients
with IBS and control subjects. These differences could potentially have
a causal relationship with the syndrome. METHODS: Microbial genomes
from fecal samples of 24 patients with IBS and 23 controls were
collected, pooled in a groupwise manner, and fractionated according to
their guanine cytosine content. Selected fractions were analyzed by
extensive high-throughput 16S ribosomal RNA gene cloning and sequencing
of 3753 clones. Some of the revealed phylogenetic differences were
further confirmed by quantitative polymerase chain reaction assays on
individual sampl es. RESULTS: The coverage of the clone libraries of
IBS subtypes and control subjects differed significantly (P <
.0253). The samples were also distinguishable by the Bayesian analysis
of bacterial population structure. Moreover, significant (P < .05)
differences between the clone libraries were found in several bacterial
genera, which could be verified by quantitative polymerase chain
reaction assays of phylotypes belonging to the genera Coprococcus,
Collinsella, and Coprobacillus. CONCLUSIONS: The study showed that
fecal microbiota is significantly altered in IBS. Further studies on
molecular mechanisms underlying these alterations are needed to
elucidate the exact role of intestinal bacteria in IBS.